Oxidation Of Fatty Acids Occurs In Mitochondria

Fatty Acids Are Transported in the Blood as Free Fatty Acids (FFA)

Free fatty acids—also called unesterified (UFA) or non-esterified (NEFA) fatty acids—are fatty acids that are in the unesterified state. In plasma, longer-chain FFA are combined with albumin, and in the cell they are attached to a fatty acid-binding protein, so that in fact they are never really "free." Shorter-chain fatty acids are more water-soluble and exist as the un-ionized acid or as a fatty acid anion.

Fatty Acids Are Activated Before Being Catabolized

Fatty acids must first be converted to an active intermediate before they can be catabolized. This is the only step in the complete degradation of a fatty acid that requires energy from ATP. In the presence of ATP and coenzyme A, the enzyme acyl-CoA synthetase (thioki-nase) catalyzes the conversion of a fatty acid (or free fatty acid) to an "active fatty acid" or acyl-CoA, which uses one high-energy phosphate with the formation of AMP and PP; (Figure 22-1). The PP; is hydrolyzed by inorganic pyrophosphatase with the loss of a further high-energy phosphate, ensuring that the overall reaction goes to completion. Acyl-CoA synthetases are found in the endoplasmic reticulum, peroxisomes, and inside and on the outer membrane of mitochondria.

Long-Chain Fatty Acids Penetrate the Inner Mitochondrial Membrane as Carnitine Derivatives

Carnitine (P-hydroxy-y-trimethylammonium buty-rate), (CH3)3N+—CH2-—CH(OH)—CH2—COO-, is widely distributed and is particularly abundant in muscle. Long-chain acyl-CoA (or FFA) will not penetrate the inner membrane of mitochondria. However, carnitine palmitoyltransferase-I, present in the outer mitochondrial membrane, converts long-chain acyl-CoA to acylcarnitine, which is able to penetrate the inner membrane and gain access to the P-oxidation system of enzymes (Figure 22-1). Carnitine-acylcar-nitine translocase acts as an inner membrane exchange transporter. Acylcarnitine is transported in, coupled with the transport out of one molecule of car-nitine. The acylcarnitine then reacts with CoA, cat-

CARNITINE

Acyl-CoA

PALMITOYL-

OUTER

SYNTHETASE

TRANSFERASE

MITOCHONDRIAL

\ I

Carnitine

Acylcarnitine

Acyl-CoA

Carnitine

Acylcarnitine

\

-^

CARNITINE PALMITOYL-TRANSFERASE II

CARNITINE ACYLCAR-NITINE TRANSLOCASE

INNER MITOCHONDRIAL MEMBRANE

Acylcarnitine

Acylcarnitine Acyl-CoA t_

Carnitine

Acylcarnitine

Acylcarnitine Acyl-CoA t_

ß-Oxidation

Figure 22-1. Role of carnitine in the transport of long-chain fatty acids through the inner mitochondrial membrane. Long-chain acyl-CoA cannot pass through the inner mitochondrial membrane, but its metabolic product, acylcarnitine, can.

alyzed by carnitine palmitoyltransferase-II, located on the inside of the inner membrane. Acyl-CoA is reformed in the mitochondrial matrix, and carnitine is liberated.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

Get My Free Ebook


Post a comment